Biologically adaptive radiotherapy for oropharyngeal Cancer (BARitOne): An R-IDEAL stage 2a-2b technical optimisation, feasibility, and safety study - Study protocol.

Abstract

BackgroundThe incidence of head and neck squamous cell cancer (HNSCC), including HPV-positive and negative oropharyngeal squamous cell cancer (OPSCC) is rising. HPV-negative and some HPV-positive OPSCC has poor outcomes. Attempts to uniformly intensify treatment in poor-prognosis HNSCC populations have been unsuccessful. Diffusion-weighted MRI (DW-MRI) has been used during radiotherapy to identify OPSCC which will fail standard radiotherapy. Biologically-adaptive, DW-MRI guided radiotherapy may allow dose-escalated radiotherapy to be delivered to populations predicted to fail standard treatment, i.e. those really in need of treatment intensification. While individual components of response-adapted workflow are not novel, their combination is significantly different. The BARitOne (Biologically Adaptive Radiotherapy for Oropharyngeal Cancer) study aims to allow optimisation and evaluate feasibility of this approach.MethodsBARitOne is a single-centre R-IDEAL stage 2a and b study of patients with poor-prognosis stage 3-4b OPSCC undergoing single-modality radical radiotherapy. All participants commence standard radiotherapy, 65Gy in 30 fractions. DW-MRI at fraction 1 and 10 assess change in apparent diffusion coefficient (ADC) in primary and nodal disease and stratify tumours into 'responders' and 'non-responders'. Non-responders receive dose-escalation (40.5Gy in 15 fractions) to the gross tumour volume (GTV) for fractions 16 to 30;total dose 73Gy in 30 fractions to GTV. Responders continue standard treatment. The primary aim is to evaluate the proportion of participants that complete DW-MRI guided response-adapted radiotherapy.DiscussionIdentifying non-responding tumours is an essential step towards individualising intensified radiotherapy for high-risk disease. The additional burden that image-guided, response-adaptive radiotherapy brings, along with the imperative to avoid gaps in radical treatment means workflow needs development and optimised prior to large-scale implementation and comparison to the current standard. BARitOne offers this, with learning also transferrable to other tumour types. While uniform treatment intensification for entire poor-prognostic HNSCC populations has failed to improve survival outcomes, this individualised and biomarker-guided approach to intensification offers an alternative strategy.Trial registrationInternational Standard Randomised Controlled Trial Number ISRCTN45653542.